Summary of Work: Apoptosis is a form of programmed cell death that occurs under numerous developmental, physiological, pathological conditions including, cancer, AIDS, autoimmune diseases and in response to environmental toxins. 1) We are studying the catabolic effectors that carry out the apoptotic process and degrade DNA, RNA, and protein during programmed death or apoptosis. We have identified and characterized one nuclease which is a member of the cyclophilin family of proteins. We have also shown that 28S ribosomal RNA is specifically degraded during apoptosis via an inherent ribonuclease that is activated when cells undergoing apoptosis shrink. 2) Apoptosis can be activated by many different signals operating through a diverse array of signal transduction pathways. We have sought to define common activation pathways for apoptosis that are independent of both the apoptotic signal and cell type. We have shown that cell shrinkage and K+ efflux must occur for caspase activation, ribosomal RNA and DNA fragmentation. Current efforts are directed towards elucidating the ion channels necessary for K+ efflux. 3) A third effort has been in the area of genetic approaches to define novel anti-apoptotic genes. Somatic cell fusion studies shown that the apoptotic phenotype is recessive and using a rescue cloning approach we have recently cloned several novel inihibitors of apoptosis. 4) We are also identifying the mechanisms of transcriptional activation of apoptosis by glucocorticorids with particular emphasis on kinases/phosphatases whose activity can affect protein phosphorylation. 5) Finally, we are evaluating the role of calcium ions in apoptosis. - Apoptosis, Aids ,Lymphocytes,Stress, Environment